An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process

Abstract

Glyphosate tolerant genetically modified (GM) maize NK603 was assessed as ‘substantially equivalent’ to its isogenic counterpart by a nutrient composition analysis in order to be granted market approval. We have applied contemporary in depth molecular profiling methods of NK603 maize kernels (sprayed or unsprayed with Roundup) and the isogenic corn to reassess its substantial equivalence status. Proteome profiles of the maize kernels revealed alterations in the levels of enzymes of glycolysis and TCA cycle pathways, which were reflective of an imbalance in energy metabolism. Changes in proteins and metabolites of glutathione metabolism were indicative of increased oxidative stress. The most pronounced metabolome differences between NK603 and its isogenic counterpart consisted of an increase in polyamines including N-acetyl-cadaverine (2.9-fold), N-acetylputrescine (1.8-fold), putrescine (2.7-fold) and cadaverine (28-fold), which depending on context can be either protective or a cause of toxicity. Our molecular profiling results show that NK603 and its isogenic control are not substantially equivalent.

Relevance of a new scientific publication (Mesnage et al., 2016†) on previous EFSA GMO Panel conclusions on the risk assessment of maize NK603

“…Uncertainty remains with regard to potential contamination of the study materials by pathogens and the related confounding effects on the study results. The publication by Mesnage et al (2016) does not reveal any new information that would invalidate the previous conclusions on maize NK603 made by the EFSA GMO Panel. Therefore, EFSA considers that the previous risk assessment conclusions on maize NK603 remain valid and applicable.…”

“…In their publication, Mesnage et al (2016) reported that maize NK603 is substantially non-equivalent to a non-GM maize comparator, and point to unintended changes in maize NK603. Mesnage et al (2016) analysed the proteomic and metabolomic profiles of maize NK603 kernels and compared those to a non-GM maize line used as a comparator.…”

“…Following a request by the European Commission, the European Food Safety Authority (EFSA) assessed the scientific publication by Mesnage et al (2016), including its relevance for the risk assessment of maize NK603.…”

“…In addition, the authors quantified the levels of expression of the CP4 EPSPS protein in maize NK603. Based on this analysis, Mesnage et al (2016) concluded that maize NK603 is compositionally non-equivalent to a non-GM maize comparator. EFSA considers that there are severe shortcomings in the experimental design, as well as uncertainties on the suitability of the test material as described by Mesnage et al (2016).…”

“…Following a request from the European Commission (EC), the European Food Safety Authority (EFSA) assessed the scientific publication by Mesnage et al (2016), including its relevance for the risk assessment of genetically modified (GM) maize NK603. Mesnage et al (2016) analysed the proteomic and metabolomic profiles of maize NK603 kernels and compared those to a non-GM maize line used as a comparator.…”